Resistance To Daunorubicin In AML Is Associated With Mutations In The TET2 Gene

Objective The present study aims to explore the association of leukemia-related genes on drug-resistance of patients with acute myeloid leukemia?AML?.Methods 54leukemia-related genes of 74 patients with newly diagnosed AML?except M3?were sequenced using next-generation sequencing technique.Results The TET2 gene had the highest mutation rate.Among these patients,11 were TET-mutant,and 5 were also accompanied with the ASXL1 mutation.The in vitro drug sensitivity assay showed that the TET2-mutant patients had a high daunorubicin resistance rate?9 cases,81.82%?,while the TET2-wild patients had a resistance rate of 6.35%?4 cases?.The difference was statistically significant.11 cases of TET2-mutant patients were treated with the DA regimen(daunorubicin 45mg/m² d1-3,cytarabine 100mg/m² d1-7),resulting in 3 CR,7 NR and 1 give up the therapy.The failure rate of the DA regimen was high,in line with the result of the in vitro drug-resistance assay.Conclusion TET2 gene mutation is associated with resistantce of AML to daunorubicin,and is a potential indicator for the therapeutic efficacy of the DA regimen.The present study showed that the TET2 gene mutations in AML were mainly the missense mutation and the rate was 14.86%,in line with other studies in the literature.Multiple studies indicated that TET2 gene mutation is a poor prognostic factor in AML patients.In the present study,the high-throughput in vitro drug sensitivity assay showed that TET2 gene mutation was related to the resistance of AML cells to daunorubicin in vitro,in line with clinical studies.This study paves the way for the in vitro drug sensitivity assay as a powerful tool for precision medicine.Further studies are needed to elucidate the mechanism behind the influence of TET2 gene mutation on daunorubicin resistance.